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Department « Cancer Biology»
Heads : Martine DEFAIS and Catherine MULLER
The main objective of this department is the identification and
validation of novel molecular targets for cancer diagnosis and
therapy. Research projects are focused both on cancer cells
themselves (with special emphasis on DNA transactions such as
transcription, replication, recombination and DNA repair) (area 1)
and on the tumour microenvironment (defined by cellular components
such as endothelial cells, lymphocytes, adipocytes and hypoxic and
nutrient-deprived conditions) (area 2). A continuum in the research
is present from molecular modelling, in vivo approaches and use of
tumour tissue specimens in collaboration with clinicians. This
department is composed of 10 teams and is taking an active part in
the structuring of Oncology research in Toulouse The research groups
involved in this department are :
Area 1 : Cancer Microenvironment : hypoxia and
nature of the stromal response into tumours
Three main topics
Mechanisms of hypoxia tolerance, regulation of the transcription
factor HIF-1 expression and function Nature of the stromal response
to tumours: phenotype of tumour-associated adipocytes, endothelial
cell phenotypes (transcription factors involved in endothelial cell
proliferation, THAP zinc finger proteins), and lymphocytes
recruitment into tumour Control of normal and leukemic
haematopoiesis, regulation of cell/matrix interaction in relation to
targeting of proteins to proteasome degradation
Significant Publications :
Ader I, Brizuela L, Bouquerel P, Malavaud B, Cuvillier O. :Sphingosine
kinase 1: a new modulator of hypoxia inducible factor 1alpha during
hypoxia in human cancer cells. (2008). Cancer Res
68 : 8635-42.
Cayrol C, Lacroix C, Mathe C, Ecochard V, Ceribelli M, Loreau E,
Lazar V, Dessen P, Mantovani R, Aguilar L, Girard JP. The THAP-zinc
finger protein THAP1 regulates endothelial cell proliferation
through modulation of pRB/E2F cell-cycle target genes. (2007).
Blood 109 : 584-594.
Heuzé ML, Lamsoul I, Baldassarre M, Lad Y, Lévêque S, Razinia Z,
Moog-Lutz C, Calderwood DA, Lutz PG. ASB2 targets filamins A and B
to proteasomal degradation. (2008) Blood
112: 5130-40.
Area 2 : Replication, transcription, DNA Repair
and recombination : molecular mechanisms of carcinogenesis and
cancer cells response to DNA damaging agents
Three main topics
Molecular basis of replication and recombination of damaged DNA,
implication in carcinogenesis and cancer progression
Characterization of DNA double-strand break repair by non-homologous
end joining Transcriptionnal regulation of DNA repair and genetic
instability
Significant Publications :
Maga G, Villani G, Crespan E, Wimmer U, Ferrari E, Bertocci B,
Hübscher U. 8-oxo-guanine bypass by human DNA polymerases in the
presence of auxiliary proteins. (2007) Nature 447 :606-8.
Oruc Z,
Boumédiène A, Le Bert M, Khamlichi AA. Replacement of Igamma3 germ-line
promoter by Igamma1 inhibits class-switch recombination to IgG3.
(2007) Proc Natl Acad Sci U S A. 104
:20484-9.
Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, Ng JM,
Dinant C, Hoeijmakers JH, Vermeulen W. Dynamic interaction of TTDA
with TFIIH is stabilized by nucleotide excision repair in living
cells. (2006). PLoS Biol. 4(6):e156.
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